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Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults

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ClinicalTrials.gov Identifier: NCT04219540
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : April 1, 2021
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:
This study seeks to compare the effectiveness of two medications used to treat opioid use disorder, extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX), among adults currently incarcerated in U.S. jails and prisons at 5 distinct trial sites. This open-label, non-inferiority, head-to-head study design will offer providers, correctional and public health authorities, payers and policy makers' timely and relevant data to assess the effectiveness of XR-B (and XR-NTX) as potentially useful re-entry and relapse prevention treatment options. It is hypothesized that XR-B is non-inferior to XR-NTX when comparing retention-in-study-medication treatment options.

Condition or disease Intervention/treatment Phase
Opioid-use Disorder Drug: XR-B (SUBLOCADETM) Drug: XR-NTX Phase 4

Detailed Description:

Participants eligible for randomization will be randomized 1:1 to extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) prior to release from the correctional controlled environment (including jails, prisons, work release and residential treatment, or other correctional facilities) and treated for 24-weeks following release or upon entry into a community CJS-mandated program.

XR-B (SublocadeTM, Indivior) is a partial opioid agonist indicated for the treatment of moderate to severe opioid use disorder. Delivered as a pre-filled 2cc subcutaneous monthly injection, typically using two 300mg/1.5 ml initial starting doses followed by 100mg/0.5 ml monthly maintenance doses. The study will provide up to six monthly XR-B doses throughout the study. Prior to an initial injection, the participant must be stable for seven days or longer on sublingual buprenorphine (SLB) at doses of 8mg/day or higher.

Description of Study Intervention Participants eligible for randomization (n=670) will be randomized 1:1 to extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) prior to release from the correctional controlled environment (including jails, prisons, work release and residential treatment, or other correctional facilities) and treated for 24-weeks following release or upon entry into a community CJS-mandated program.

XR-B (SublocadeTM, Indivior) is a partial opioid agonist indicated for the treatment of moderate to severe opioid use disorder. Delivered as a pre-filled 2cc subcutaneous monthly injection, typically using two 300mg/1.5 ml initial starting doses followed by 100mg/0.5 ml monthly maintenance doses. The study will provide up to six monthly XR-B doses throughout the study. Prior to an initial injection, the participant must be stable for seven days or longer on sublingual buprenorphine (SLB) at doses of 8mg/day or higher.

XR-NTX (Vivitrol®, Alkermes) is an opioid antagonist indicated for the prevention of opioid dependence, following detoxification. A negative opioid urine toxicology, negative self-report of any recent opioid use, and a naloxone challenge. The naloxone challenge consists of 0.4-0.8mg of IV/SC/IM naloxone followed by the observation of no opioid withdrawal symptoms, or the use of oral naltrexone (12.5-25mg) followed by 1-2 hours of observation. XR-NTX is delivered as a 380mg (4cc) intramuscular injection to the upper outer gluteus (buttock) monthly. The study will provide six or more monthly XR-NTX doses.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 301 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults
Actual Study Start Date : January 7, 2021
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: extended-release buprenorphine (XR-B)
Subjects who agree to XR-B treatment will receive an XR-B injection to the abdomen. The injection is a liquid medication in the amount of either 100 or 300 mg buprenorphine in 1.5 cc volume and will last in the body for about 30 days. The medication is stored in a small nodule under the skin of the belly where it was injected. The buprenorphine is gradually released into the body over time for a 30-day period.
Drug: XR-B (SUBLOCADETM)
XR-B (SUBLOCADETM) contains buprenorphine, a partial opioid agonist, and is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. Following induction and dose adjustment with sublingual buprenorphine, the recommended starting dose is 300 mg monthly for the first two months followed by a maintenance dose of 100 mg monthly thereafter. XR-B is administered monthly only by subcutaneous injection in the abdominal region. Study clinical staff will have flexibility to continue the 300mg dose for greater than 2 months, or use the 100mg dose for initial induction, if the participant's opioid use history or clinical status at the time of dosing support these decisions.
Other Name: SUBLOCADE TM

Experimental: extended release naltrexone XR-NTX
Subjects who agree to XR-NTX treatment will receive an injection of XR-NTX to the outer upper part of your buttock. The injection is a liquid medication in the amount of 380 mg naltrexone in 4 cc volume (about 1 teaspoon) and will last in your body for about 30 days. Following release, visits with study physicians at Bellevue Hospital will offer further counseling or medication treatment referrals, the option to receive additional XR-NTX injections once a month following the first injection and continued encouragement to avoid relapses and stay on treatment.
Drug: XR-NTX
XR-NTX (Vivitrol®) produces a 30-day mu opioid receptor antagonist blockade Induction procedures require detoxification off opioids (5-7 days since last opioid use), a negative opioid urine toxicology, negative self-report of any recent opioid use, and a naloxone challenge. The naloxone challenge consists of 0.4-0.8mg of IV/SC/IM naloxone followed by the observation of no opioid withdrawal symptoms, or the use of oral naltrexone (12.5-25mg) followed by 1-2 hours of observation. XR-NTX is then delivered as a 380mg (4cc) intramuscular injection to the upper outer gluteus (buttock). Study interventions are FDA-approved, used in accordance with FDA-labeling and will be administered by a study clinician
Other Name: Vivitrol®

No Intervention: Treatment as Usual (TAU)
In this group you will not receive any study medication. You will be able to receive any treatments available to individuals in the jail or prison who are not in the study. Trained study staff at the first two visits will provide counseling focusing on relapse and overdose prevention, treatment engagement, and navigating re-entry challenges.



Primary Outcome Measures :
  1. Change in effectiveness of XR-B versus XR-NTX [ Time Frame: Weeks 1-24 ]
    The primary outcome measure is the number of injections during the 24-week post-release treatment phase, range 0-6. The comparison of the two arms will be based on the log-odds ratio of the injection rate for participants randomized to XR-B vs. XR-N. Retention is defined as the proportion of scheduled study medication injections received (range, 0-6). For the primary outcome, less than 6 XR-B injections will contribute to lower retention (<5 of 6), and 7+ XR-NTX will contribute only to maximum retention (6 of 6).


Secondary Outcome Measures :
  1. Change in Opioid use [ Time Frame: Weeks 0, 4, 8, 12,16, 20, 24, 52 ]
    Change in opioid treatment outcomes will assess for illicit opioid use through self-reported opioid use (days per month), opioid-positive urine samples (negative vs. positive or missing, monthly), and overdose events (fatal and non-fatal),

  2. Change in Opioid treatment outcomes - adverse events [ Time Frame: Weeks 0, 4, 8, 12,16, 20, 24, 52 ]
    Change in Opioid use will be tracked monthly through non-fatal and fatal overdose events and other adverse events and death recorded on the Opioid Overdose AE form and the Opioid relapse outcome form.

  3. Change in Opioid treatment outcomes - lifestyle changes [ Time Frame: Weeks 0, 4, 8, 12,16, 20, 24, 52 ]
    Non-study addiction treatment participation, depression scores (Hamilton Depression scale) and quality of life (WHOQOL) changes will be assessed for demographic, housing, employment status changes.

  4. Change in Opioid treatment outcomes - HIV changes [ Time Frame: Weeks 0, 24 ]
    Changes in HIV sex and IVDU risk scores as well as HIV and HCV status will be assessed HIV/HCV risk behaviors (RAB), HIV P24ag/ ab with reflex HIV RNA (if HIV ab negative at baseline; if HIV AB positive at baseline just check HIV RNA) and HCVAb with reflex HCV RNA if AB positive ( if AB + at baseline then just HCV VL at f/u timepoints) at baseline week 24 and week 52

  5. Change in criminal justice system (CJS) involvement with XR-B versus XR-NTX [ Time Frame: Weeks 4, 8, 12,16, 20, 24, 52 ]
    Criminal justice system (CJS) involvement and recidivism outcomes will be measured by the number of new criminal charges, new arrests, re-incarceration episodes, and re-incarceration days by CJS public records audits. XR-B may be an effective CJS intervention alongside other OUD medications and may ultimately allow for much wider uptake of opioid agonist medication treatments in CJS populations in comparison to XR-NTX.

  6. Change in Non-randomized Treatment-As-Usual retention compared to XR-B/XR-N. [ Time Frame: Weeks 4, 8, 12,16, 20, 24, 52 ]
    TAU participants in this trial will be followed similarly to randomized participants but will not receive study medication or active medical treatment from the study. Prior to release from correctional controlled environment and at research visit follow-up in the community, all TAU participants will be provided education and materials that include information on opioid overdose prevention and referrals to other community addiction treatment services. TAU participants will receive the same visit incentives and study team contact, including Tracker services, as randomized participants. This amount of contact, incentives, education, and referrals are likely in excess than actual real-world 'usual care' of opioid use disorder patients released from a CJS controlled environment, and is in keeping with ethical standards for clinical trials among prisoners, in which all experimental arms must receive some tangible yet non-coercive benefit beyond usual care.

  7. Change in Non-randomized Treatment-As-Usual rates of OUD [ Time Frame: Weeks 4, 8, 12,16, 20, 24, 52 ]
    TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications. TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

XR-B vs. XR-NTX Inclusions:

  1. Adult volunteer aged 18-65yo able to provide written informed consent in English (or Spanish at some sites)
  2. Current CJS incarceration (residing in a controlled environment) with pending release date (within 6 months of randomization)
  3. Current or history of moderate-to-severe opioid use disorder in the past year prior to incarceration (OUD, DSM-5)
  4. Not planning to move out of state or to new location within 6-months post-release.
  5. Willing to accept either XR-B or XR-NTX assignment.

Non-randomized TAU Inclusions:

  1. Recruited prior to launch of RCT or not willing to randomize to XR-B or XR-NTX assignment, but are otherwise eligible based on inclusion (#2-4) and exclusion below (#6-10)
  2. Adult volunteer aged 18-65yo able to provide written informed consent in English or Spanish
  3. Current CJS incarceration with pending release date
  4. Current or history of moderate-to-severe opioid use disorder in the past year prior to incarceration (OUD, DSM-5)
  5. Not planning to move out of state or to new location within 6-months post-release.

    Exclusion Criteria:

    XR-B vs. XR-NTX Exclusions:

  6. Medical or psychiatric disorders making participation unsafe or regular follow-up unlikely, (such as suicidal ideation or pre-existing moderate to severe hepatic impairment)
  7. Pregnancy, planning conception, or breast-feeding
  8. Allergy, hypersensitivity or medical contraindication to either medication
  9. Chronic pain requiring opioid pain management
  10. On daily stable methadone or buprenorphine (SL-B) maintenance every day for past 30 days prior to incarceration or monthly XR-NTX or XR-BUP one month prior to incarceration AND intending to remain on methadone or buprenorphine or XR-NTX maintenance upon return to the community.

Non-randomized TAU Exclusions:

6. Severe medical or psychiatric disorders, such as suicidal ideation or moderate to severe hepatic impairment 7. Pregnancy, planning conception, or breast-feeding 8. Allergy, hypersensitivity or medical contraindication to either medication 9. Chronic pain requiring opioid pain management 10. On daily stable methadone or buprenorphine (SL-B) maintenance every day for past 30 days prior to incarceration or monthly XR-NTX or XR-BUP one month prior to incarceration AND intending to remain on methadone or buprenorphine or XR-NTX maintenance upon return to the community.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04219540


Contacts
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Contact: Mia Malone 646-501-3577 Mia.malone@nyulangone.org
Contact: Ryan McDonald 646-501-3581 Ryan.mcdonald@nyulangone.org

Locations
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United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Contact: Sandra Springer, MD       sandra.springer@yale.edu   
Principal Investigator: Sandra Springer, MD         
United States, Maryland
Friends Research Institute Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Robert Schwartz, MD       rschwartz@friendsresearch.org   
Principal Investigator: Robert Schwartz, MD         
United States, New Hampshire
Dartmouth College Not yet recruiting
Hanover, New Hampshire, United States, 03755
Contact: Lisa Marsch, PhD       Lisa.A.Marsch@dartmouth.edu   
Principal Investigator: Lisa Marsch, PhD         
United States, New Jersey
Rutgers University Not yet recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Amesika Nyaku, MD       ann37@njms.rutgers.edu   
Principal Investigator: Amesika Nyaku, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Mia Malone       Mia.malone@nyulangone.org   
Principal Investigator: Joshua Lee, MD, MSc         
United States, Oregon
Oregon Health and Science University Not yet recruiting
Portland, Oregon, United States, 97219
Contact: Elizabeth Waddell, PhD       waddelle@ohsu.edu   
Principal Investigator: Elizabeth Waddell, PhD         
Sponsors and Collaborators
NYU Langone Health
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Joshua Lee, MD NYU Langone
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT04219540    
Other Study ID Numbers: 19-01450
First Posted: January 7, 2020    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Immediately following publication. No end date.
Access Criteria: Researchers who provide a methodologically sound proposal. Upon reasonable request. Requests should be directed to mia.malone@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Buprenorphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists